Hernando Lyons

Induction of Gastric Ornithine Decarboxylase in Early Weaning Rats

Background/Aims: Early weaning has been shown to induce intestinal ornithine decarboxylase (ODC) activities and cell proliferation in rats. No information is available about the effect of early weaning on ODC activity in the stomach. Methods: Suckling rats were prematurely weaned on postnatal day 15 and followed through day 21. Oxyntic gland mucosa of stomach was obtained on postnatal days 15, 16, 18 and 21 (days 0, 1, 3 and 6 after early weaning) and assayed for ODC activity, DNA, protein and pepsinogen activity. α-Difluoromethyl ornithine (DFMO), a specific ODC inhibitor, was given orally to early-weaned pups and its resultant effects were assessed on days 1 and 6 after early weaning. Results: Stomach mucosal wet weight, DNA, protein and pepsinogen activities significantly increased on day 6 after early weaning. ODC activity increased on days 1, 3, and 6 after early weaning, with the highest increase (3-fold) on day 1 when compared to controls. The increases of ODC activity, DNA and protein contents as induced by early weaning were significantly suppressed when pups were exposed to DFMO. However, no suppression of pepsinogen activity was observed. Conclusions: Our study shows that early weaning induces ODC activity and functional growth in the stomach. Gastric ODC activity is essential in gastric mucosal growth processes but not in differentiation. The induction of stomach ODC may act as an early marker in the growth of stomach mucosa induced by early weaning in rats.

Outcomes after laparoscopic cholecystectomy in children with biliary dyskinesia.

Our objectives were to determine the prevalence of biliary dyskinesia (BD) as an indication for cholecystectomy in children and to identify presenting clinical findings and optimal ejection fraction (EF) associated with the resolution of symptoms after surgery. We conducted a retrospective review of medical records of 212 pediatric patients who underwent cholecystectomy from August, 1998 to November, 2006. Patients who met criteria for BD had their short-term outcomes examined by record review and their long-term postoperative outcomes recorded by questionnaire. To compare EF and clinical presentation to symptom resolution or outcome, &khgr;2 tests were used. Logistic regression was used to evaluate possible predictors of symptom resolution. BD was the indication for cholecystectomy in 20% of patients (44 of 212). Short-term outcome was not predicted by any of the collected variables. An EF ⩽11% predicted higher rate of symptom resolution (P=0.02). Although patients with specific right upper quadrant pain had higher rates of long-term improvement than those with nonspecific abdominal pain (57.9% vs. 18.2%), this did not reach significance (P=0.057). The only predictor emerging from the logistic regression was EF cutoff at 11% (odds ratio=17.5; 95% confidence interval, 1.756-174.418). In this series, symptoms of BD were more likely to be resolved by cholecystectomy in children with EF ⩽11%.

Eosinophilic esophagitis associated with celiac disease in children

BackgroundCeliac disease (CD) and eosinophilic esophagitis (EoE) are distinct diseases of the gastrointestinal tract with specific clinico-pathological characteristics. Recent studies have found higher rates of EoE in patients with CD than in the general population. Our aim was to estimate the incidence of EoE among children who were diagnosed with CD over a 42-month period.MethodsThe study included patients diagnosed with CD based on endoscopy and histopathological findings between January 2010 and June 2013. Histopathology reports of esophageal biopsies were reviewed to identify all cases of EoE. The patients’ presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, treatments, and follow-ups were analysed.ResultsFifty-six patients with CD were identified, of whom six (10.7%) were diagnosed with both CD and EoE. Four of these patients presented with abdominal pain and diarrhea, two presented with failure to thrive, and three presented with food allergies. Endoscopic and histopathological changes typical of EoE were observed in all six patients. During follow-up, two patients showed significant improvement with the gluten-free diet and a proton-pump inhibitor (PPI). Two patients improved with the elimination diet and two patients were treated with topical corticosteroid therapy. Endoscopic appearance was normal in all children on follow-up endoscopy after treatment. Biopsy samples also showed resolution of the histologic features of EoE in all of the children.ConclusionThe incidence of EoE in our cohort of children with CD was 10.7%, which is higher than what has been reported for the general population. In all children undergoing upper gastrointestinal endoscopy for suspected CD, coexistence of EoE should be considered.

MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile‐onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17‐related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early‐onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late‐onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.

Lysosomal acid lipase deficiency in all siblings of the same parents

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.

2001: Author Index for abstracts

Babyatsky, M.W. 272 Baffi, M.C. 273 Ball, A.J. 269 Ballinger, A.B. 273 Bantick, S. 254 Barbara, G. 254 Barrachina, M.D. 271 Beckett, E.A.H. 250 Beckmann, C. 254 Bellinger, L.L. 252 Bielanski, W. 270 Bielefeldt, K. 267, 274 Bilski, J. 262 Bischoff, S. 251 Bonaz, B. 274, 275 Bonior, J. 262, 273 Booth, C.E. 267 Bradley, J.M. 249 Brammer, M.J. 254 Brinkman, B. 264 Brodacz, B. 270 Brown, D.R. 271 Browning, K.N. 272 Bruijnzeel, A.W. 277 Brzozowski, T. 261, 270 Bueno, L. 274, 275 Burr, R.L. 276 Burton, D. 264